Recently processes for the purification of tissue plasminogen activator (hereinafter referred to as TPA) with the use of an adsorbent wherein a ligand having an affinity for TPA is attached to a water-insoluble carrier have been developed.
For example, fibrin/Sepharose (see Per Wallen et al., Biochimica Biophsica Acta, 719, 318-328, 1982) and concanavalin A/agarose (see Dingeman C. Rijken et al., The Journal of Biological Chemistry, 256, No. 1, 7035-7041, 1981) each prepared by adsorbing a substrate of TPA in vivo as a ligand by a carrier have been devloped. There have been further developed processes for the purification of TPA with polyclonal and monoclonal antibodies of TPA/Sepharose by taking advantage of the affinity of an antigen to an antibody (see P.A. Andreasen et al., The EMBO Journal, 3, No. 1, 51-56, 1984: and L.S. Nielsen et al., ibid, 2, No. 1, 115-119, 1983).
Furthermore there has been known a process for the purification of TPA with an affinity resin by using a low molecular weight compound as a ligand such as arginine/Sepharose (see M. Ronby et al., Febs Letters, 146, No. 2, 289-292, 1982). However this process suffers some disadvantages. That is, the affinity of the arginine/Sepharose to TPA is not so high that the purification of TPA from its crude solution might not be readily carried out. Therefore a pretreatment with chromatographic techniques is required. In addition, this process gives an insufficient yield.